Over the past fifteen years, angiotensin converting enzyme inhibitors (ACE-I) have proven to be potent anti-hypertensive agents. Studies have shown that oral administration of an ACE-I to spontaneously hypertensive rats (SHR) during the developmental stages of hypertension can prevent elevations in arterial pressure. Additionally, the anti-hypertensive effects of ACE-I persist in the SHR for several months following cessation of therapy. Presently, the exact mechanism(s) involved in the sustained anti- hypertensive effects of ACE-I following withdrawal of treatment have not been determined. Both clinical and experimental forms of treatment have not been determined. Both clinical and experimental forms of hypertension are associated with endothelial dysfunction. In the SHR, acetylcholine-induced relaxation is severely impaired and serotonin- induced constriction is increased. Reports from our laboratory as well has others have shown that oral administration of an ACE-I can remarkably improve endothelial function in the SHR. Further, utilizing an in vitro blood vessel bioassay, we were the first to document that aortic rings from SHR treated with the ACE-I captopril followed by a period of withdrawal exhibited increased endothelium-dependent relaxation to acetylcholine and decreased contractile responses to serotonin. Additionally, our preliminary data suggest that early ACE-I treatment and its withdrawal prevents altercations in vascular morphology associated with hypertension in SHR. Based on these observation. We hypothesize that the prolonged anti-hypertensive effects of early ACE-I treatment are related to its sustained protective effect on the function of the vascular endothelium and vessel structure in association with an altercation in the vascular renin angiotensin system. To test this hypothesis, we will determine the effects of the ACE-I treatment and its withdrawal on the expression of the genes for the renin angiotensin system in vascular tissue, morphology of the vascular tissue, morphology of the vascular intima and define the nature of the relationship between structural altercations of the vascular intima and endothelium-dependent responses.